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Functional analysis of voltage-gated sodium channel in anesthesia mechanism using dorsal root ganglion cells

Research Project

Project/Area Number 19K09382
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionJichi Medical University

Principal Investigator

MINAMI KOUICHIRO  自治医科大学, 医学部, 講師 (70279347)

Co-Investigator(Kenkyū-buntansha) 堀下 貴文  産業医科大学, 医学部, 教授 (40369070)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords局所麻酔薬 / Nav1.7 / オピオイド受容体(OR) / バニロイド受容体サブタイプ3 / 麻酔薬 / 鎮痛薬 / カルバクロール / 電位依存性Naチャネル(Nav) / オピオイド受容体 / TRPV3 / リドカイン / メピバカイン / ロピバカイン / 電位依存性Na+チャネル / オピドイド受容体 / G蛋白共役型受容体 / アフリカツメガエル卵母細胞発現 / 培養脊椎後根神経節細胞 / TRP / 培養脊髄後根神経節細胞 / アフリカツメガエル卵母細胞発現系 / ナトリウム チャンネル / オピオイド / 脊椎後根神経節細胞 / アフリカツメガエル卵母細胞
Outline of Research at the Start

麻酔・鎮痛薬の薬理機序は未だに解決されていない。中枢神経系には多くのモルヒネの作用するオピオイド受容体が数多く存在し、疼痛、麻酔、鎮痛機序に関係している。一方、電位依存性Naチャネルへ(Nav)の麻酔薬、鎮痛薬の影響は十分に知られていない。最近、Nav1.7が欠損すると生涯にわたる内因性の痛覚消失が引き起こされるという報告がなされ、Navとオピオイドの疼痛機序における関係性が注目されている。本研究ではNavとμオピドイド受容体への麻酔薬・鎮痛薬の作用を培養脊椎後根神経節細胞とアフリカツメガエル卵母細胞発現系で明らかにする。

Outline of Final Research Achievements

In this study, the effects of anesthetics and analgesics on Nav1.7 and opioid receptors (OR) were analyzed in cultured dorsal root ganglion cells and African turkey oocytes expression system. Although preliminary results were obtained during this study period, the direct relationship between Nav1.7 and the action of OR was not completely analyzed. However, we revealed a non-competitive inhibitory effect of local anesthetics on the transient receptor potential vanilloid receptor subtype 3 (TRPV3) channel, which is one of the mechanisms of action of local anesthetics. Local anesthetics inhibited the 2APB activation current from the TRPV3 channel in a concentration-dependent manner. These inhibitions were not mediated by the intracellular signaling cascade. This result was considered to be one of the mechanisms of action of local anesthetics.

Academic Significance and Societal Importance of the Research Achievements

本研究ではNav1.7とオピオイド受容体(OR)への麻酔薬・鎮痛薬の作用を培養脊髄後根神経節細胞とアフリカツメガエル卵母細胞発現系で解析した。本研究は電位依存性ナトリウムチャネルの鎮痛機序への関与の一部を明らかにするものであり、社会的な意義があると考えられる。また、今回一過性受容体電位バニロイド受容体サブタイプ3(TRPV3)チャネルに対する局所麻酔薬の非競合的阻害効果を明らかにした。本結果は局所麻酔薬の作用機序の一つと考えられ、今後の研究の発展に繋がると考えられた。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (4 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] Local Anesthetics Inhibit Transient Receptor Potential Vanilloid Subtype 3 Channel Function in Xenopus Oocytes2021

    • Author(s)
      Reiko Horishita, Yuichi Ogata, Ryo Fukui, Ryo Yamazaki, Kuniaki Moriwaki, Susumu Ueno, Nobuyuki Yanagihara, Yasuhito Uezono, Yuka Yokoyama, Kouichiro Minami, Takafumi Horishita
    • Journal Title

      Anesth Analg

      Volume: 1756-1767 Issue: 6 Pages: 1756-1767

    • DOI

      10.1213/ane.0000000000005546

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carvacrol inhibits the neuronal voltage-gated sodium channels Nav1.2, Nav1.6, Nav1.3, Nav1.7, and Nav1.8 expressed in Xenopus oocytes with different potencies2020

    • Author(s)
      Horishita Takafumi、Ogata Yuichi、Horishita Reiko、Fukui Ryo、Moriwaki Kuniaki、Ueno Susumu、Yanagihara Nobuyuki、Uezono Yasuhito、Sudo Yuka、Minami Kouichiro
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 142 Issue: 4 Pages: 140-147

    • DOI

      10.1016/j.jphs.2019.12.009

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways2019

    • Author(s)
      Miyano Kanako、Shiraishi Seiji、Minami Koichiro、Sudo Yuka、Suzuki Masami、Yokoyama Toru、Terawaki Kiyoshi、Nonaka Miki、Murata Hiroaki、Higami Yoshikazu、Uezono Yasuhito
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 13 Pages: 3271-3271

    • DOI

      10.3390/ijms20133271

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 止痢薬ロペラミドは温度感受性TRPチャネルファミリー,TRPM8機能を抑制する2020

    • Author(s)
      福井遼,緒方裕一,森脇邦明,堀下玲子,堀下貴文
    • Organizer
      日本麻酔科学会第67回学術集会
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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